【摘要】 目的通过对荷瘤小鼠进行以腺病毒为载体的可溶性血管内皮生长因子型受体(solublevascularendothelialgrowthfactorreceptor-2,sFLK-1)基因治疗联合伽玛刀治疗,了解两者的协同治疗作用。方法构建表达sFLK-1基因的腺病毒,在293细胞中扩增、纯化、鉴定。建立负载大鼠C6胶质瘤细胞的BALB/c裸小鼠的动物模型,实验分为空载病毒组、重组腺病毒组、伽玛刀组、重组腺病毒+伽玛刀联合治疗组,肿瘤细胞接种后12d(体积增至约110mm3)联合治疗组及伽玛刀组应用伽玛刀(13Gy)对荷瘤小鼠进行治疗;肿瘤细胞接种后7、14d联合治疗组及重组腺病毒组尾静脉注射重组腺病毒(Ad-sFLK-1)1×109PFU;观察荷瘤小鼠存活率,测量肿瘤大小,免疫组化法测肿瘤组织微血管密度,Tunel法检测凋亡小体。结果联合治疗组不仅能明显抑制肿瘤组织的生长,而且能明显延长小鼠的生存期,与其他三组比较减少肿瘤组织中微血管密度,Tunel法显示凋亡小体明显增多,P均<0.05。结论对负载大鼠C6胶质瘤细胞的荷瘤小鼠,sFLK-1基因治疗联合伽玛刀能够抑制小鼠肿瘤生长和肿瘤血管生成,起到协同作用。更多还原

【Abstract】 Objective To evaluate whether the sustained expression by adenovirus-mediated gene (sFLK-1)transfer can enhance the treatment efficacy of gamma knife radiosurgery. Methods The mouse sFLK-1 gene was cloned to construct the recombinant adenovirus. The gliomata growing in BALB/c female nude mice with an initial mean volume of (109.3±20.5) mm~3 were treated with gamma knife alone (13 Gy on day 12), sFLK-1 adenovirus alone (1×10~9 plaque-forming units, PFU was given to two mouse tail vein by injections, 7 and 14 days), gamma knife associated with sFLK-1 adenovirus or control adenovirus (1×10~9 PFU was given to two mouse tail vein by injections, 13 and 17 days). After the completion of therapy, the tumor size was recorded. The microvessel density (MVD) and tumor apoptosis were evaluated by immunohistochemical means. Results As comparing with three other control groups, the combination treatment group with sFLK-1 gene therapy and gamma knife not only significantly reduced tumor volume and prolonged the life span of tumor burden mice as well. In addition, the average tumor weights were lower in sFLK-1 combined with gamma knife group than in any other control group. Immunohistochemical analysis of glioma demonstrated a decreased MVD and a high apoptosis cell rate in sFLK-1 combined with gamma knif group. Conclusion The antitumor effect of gamma knife can be potentiated by sFLK-1 gene therapy. Thus the combination of sFLK-1 gene therapy and gamma knife results an additive effect of antitumor. The observation may provide an important strategy for treatment cancer metastasis.更多还原